Jim Cypser Institute for Behavioral Genetics Campus Box 447 University of Colorado at Boulder Boulder, Colorado 80309-0447 Phone 303-492-5159 Fax 303-492-8063 email: James.Cypser@Colorado.EDU Personal Home Page my C.V.

Research Interests:

I'm interested in the relationship between stress resistance and life span. I use the nematode Caenorhabditis elegans as a model organism to investigate the effects of single gene mutations, caloric restriction, and adaptive stress resistance (hormesis) on life extension.

I've established that there is an additive effect on life span between age-1 and a second gerontogene which does not appear to be a part of the insulin/IGF pathway, suggesting a novel pathway for life extension. The double mutants live significantly longer than would be expected from a strictly additive effect.

I have extensively characterized stress resistance and life extension induced by sub lethal stress pretreatments in the worm, including recent work that suggests particular genes are required for the observed life extension. I am currently trying to establish what period of the life span displays reduced mortality in response to heat pretreatments that increase average life span. A second goal of these experiments will be to test whether the induced thermotolerance coincides with the induced reduction of mortality; this will address whether the relationship between life extension and stress resistance is causal or merely correlative.

I am also interested in whole-genome analysis of the transcriptional regulatory responses to life-extending effects. To this end I have used C. elegans DNA micro array data to compare the expression levels of 17,722 genes in long-lived mutants versus animals with wild-type life span. I found 887 genes to be differentially expressed at a significance level of p < .01 (independent t-test of the means) between the two groups; that is, five times as many as would be expected by chance alone. The top 100 most significant genes include several that may be involved in glycolysis and the stress response. I hope to extend this analysis using new data from worms that have been heat pretreated and calorically restricted.

Jim Cypser